Medicolegal Issues

In the Literature


In This Edition

Literature at a Glance

A guide to this month’s studies

Clinical Shorts


A prospective observational study showed that for all 23 patients with malignant pleural effusions, the cytology was identical for the 50 mL specimen when compared with the large-volume specimen (~890mL). Large specimens also demonstrated the same yield for detecting negative cytology.

Citation: Abouzgheib W, Bartter T, Dagher H, Pratter M, Klump W. A prospective study of the volume of pleural fluid required for accurate diagnosis of malignant pleural effusion. Chest. 2009;135(4):999-1001.


In an observational study to evaluate the duration of colonization in patients colonized with methicillin-resistant Staphylococcus aureus (MRSA), 48.8% of patients remained colonized at one year (95% CI, 45.8-51.7%) and 21.2% at four years (95% CI, 13.1-31.4%).

Citation: Robicsek A, Beaumont JL, Peterson LR. Duration of colonization with methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2009;48(7):910-913.


Analysis of genomewide association data generated from four large cohort studies of incident stroke found a genetic locus on chromosome 12p13 associated with an increased risk of stroke.

Citation: Ikram MA, Seshadri S, Bis JC, et al. Genomewide association studies of stroke. N Engl J Med. 2009;360(17):1718-1728.


This retrospective, single-center analysis showed that patients with moderate chronic kidney disease (eGFR of 15 to 59 mL min(-1) 1.73 m(-2)) and proteinuria (> or equal to 30 mg/dL) were associated with increased risk for stent thrombosis, nonfatal myocardial infarction (MI), and higher all-cause mortality in patients with an acute MI.

Citation: Lambert ND, Sacrinty MT, Ketch TR, et al. Chronic kidney disease and dipstick proteinuria are risk factors for stent thrombosis in patients with myocardial infarction. Am Heart J. 2009;157(4):688-694.


This prospective cohort study of patients with known infectious endocarditis found that the modern presentation tends to be earlier in the disease course and associated with fevers. However, fewer of the other traditional stigmata of infective endocarditis are present. Staphylococcus aureus has become the dominant organism and mortality remains high.

Citation: Murdoch DR, Corey GR, Hoen B, et al. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis—Prospective Cohort Study. Arch Intern Med. 2009;169(5):463-473.


A retrospective cohort study of patients undergoing coronary artery bypass grafting (CABG) compared the risk of perioperative infection in patients on clopidrogrel and aspirin with patients on neither agent. The study found that patients on these medications have a significantly increased risk of perioperative infection.

Citation: Blasco-Colmenares E, Perl TM, Guallar E. Aspirin plus clopidrogrel and risk of infection after coronary artery bypass surgery. Arch Int Med. 2009;169(8):788-796.


Prospective observational evaluation shows that physical examination of peripheral perfusion identifies patients with significantly higher odds of worsening organ failure and higher lactate levels following initial resuscitation.

Citation: Lima A, Jansen TC, van Bommel J, Ince C, Bakker J. The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med. 2009;37(3):934-938.

Pulmonary Embolism Frequently Complicates COPD Exacerbations

Clinical question: What percentage of patients with acute chronic obstructive pulmonary disease (COPD) exacerbations has pulmonary emboli?

Background: As many as 30% of COPD exacerbations have no apparent precipitating event. Even in patients with evidence of a precipitating event, such as an upper-respiratory illness or increased environmental irritants, pulmonary emboli (PE) may coexist and warrant evaluation.

Study design: Literature review.

Setting: Multiple studies in Europe and the U.S.

Synopsis: This literature review included five studies to estimate the rate of PE in patients with a COPD exacerbation. Overall incidence of PE in COPD exacerbations was 19.9%, but of those patients requiring hospitalization, the incidence was as high as 25.5%. Incidence estimates varied based on interpretation of data that were missing or inconsistent between studies. Patients most commonly present with dyspnea, chest pain, hemoptysis, cough, and palpitations. Six percent of PE patients presented with syncope; no patients with an exacerbation without a PE presented with syncope.

Risk of mortality from PE is almost twice as high in patients with a COPD exacerbation compared with PE in other settings. A significant number of patients have PE without history or evidence of DVT, so in situ thrombosis is a significant factor. The interpretation of these results is limited by the heterogeneity of the study designs, and by the relatively low number of cases. Larger trials are necessary.

Bottom line: Pulmonary emboli are present in as many as 25% of all COPD exacerbations. Delay in diagnosis of PE in COPD patients affects morbidity and mortality. PE should be a consideration in many COPD exacerbations.

Citation: Rizkallah J, Man SF, Din DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

Targeted-Care Bundle Can Reduce ED Visits and Readmission Rates in High-Risk Elderly Patients

Clinical question: Can a care coordination bundle reduce length of stay (LOS), ED visits, or readmissions within 30 days of a hospital admission?

Background: Hospital-based care coordination interventions have shown mixed results in affecting LOS, post-discharge ED visits, and readmission rates. Although there has been some success with particular interventions, no consistent benefit has been demonstrated. Most notably, a recent meta-analysis of several different interventions showed no improvement in mortality, LOS, or readmission rates.

Study design: A randomized, controlled trial of select high-risk elderly patients.

Setting: A large teaching hospital at Baylor University Medical Center.

Synopsis: A “targeted-care bundle” was implemented with high-risk elderly patients to try to reduce LOS, readmissions, and ED visits. High-risk patients were identified by age, diagnosis-related group (DRG), number of medications at admission, comorbid conditions, and need for assistance in activities of daily living. Subjects were randomized to usual care or to receive a targeted-care bundle. The targeted-care bundle included multiple interventions. A study care coordinator provided daily patient education, including condition-specific teaching, discharge teaching and planning, and a follow-up phone call at five to seven days after discharge. A clinical pharmacist intervened for medication reconciliation at admission and discharge, medication teaching, and a follow-up phone call at five to seven days after discharge. Structured documents, including a personal health record and supplemental discharge form, were implemented.

The study had low enrollment, largely due to the requirement to obtain informed consent from all participants. Therefore, the study was underpowered to detect such target endpoints as LOS. A significant decrease in 30-day readmission rates/ED visits was noticed, but there was no persistent effect at 60 days.

The intervention was designed to use existing hospital staff in order to be practical for broad utilization. Future studies need to focus on increased enrollment to demonstrate beneficial effect.

Bottom line: Targeted health interventions focusing on education and coordination of care might effect some significant outcomes, most notably readmissions or ED visits within 30 days, but the nature of the clinical problem makes rigorous testing of interventions a challenge.

Citation: Kohler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.

Family History Is a Risk Factor for Venous Thrombosis

Clinical question: Is family history of additional value in predicting an individual’s risk of venous thrombosis once a genetic risk factor is identified?

Background: A positive family history of venous thrombosis might suggest the presence of genetic risk factors in a given family. However, it is not known whether family history is of additional significance—once a risk factor is identified—in predicting an individual’s risk for venous thrombosis.

Study design: Population-based, case-control study.

Setting: Participants in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study.

Synopsis: Recruitment, data collection, and blood samples were obtained from individuals in the MEGA study. Participants completed a questionnaire about risk factors for venous thrombosis and family history. A positive family history more than doubled the risk of venous thrombosis, and when more than one family member was affected, the risk increased fourfold. The risk for venous thrombosis increased 64 times for individuals who had a family history, genetic risk factor, and environmental risk factor when compared with those with a negative family history and no known risk factors.

The underreporting or overestimation of the prevalence of a positive family history might limit this study.

Bottom line: Family history is a risk indictor for a first venous thrombosis, despite the presence of other risk factors.

Citation: Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169(6):610-615.

Vasopressor Choice Predicts Mortality in Septic Shock

Clinical question: Does vasopressor choice affect mortality in patients with community-acquired septic shock?

Background: Community-acquired septic shock is a common illness and, despite aggressive care, a leading cause of death. Randomized clinical control trials evaluating the efficacy and safety of different adrenergic supportive agents are lacking. Thus, both norepinephrine and dopamine are recommended as first-line agents in the treatment of septic shock by the Surviving Sepsis Campaign guidelines.

Study design: Multicenter, cohort observational study.

Setting: Seventeen intensive-care units in Portugal.

Synopsis: In adjusted analysis controlling for Simplified Acute Physiology Score (SAPS) II, use of norepinephrine in community-acquired septic shock was associated with higher hospital mortality and lower 28-day survival when compared with dopamine. Specifically, patients treated with norepinephrine had a statistically significant higher hospital mortality rate than those treated with dopamine (52% and 38.5%, respectively, P=0.002) and a lower 28-day survival (log rank=22.6; P<0.001). While this data is valuable, the nonrandomized, observational study design limits firm conclusions regarding vasopressor choice. Further results from three large trials comparing vasopressor use in septic shock should continue to shed light on this debate.

Bottom line: Norepinephrine administration is associated with higher hospital mortality and lower 28-day survival when compared with dopamine in patients with community-acquired septic shock.

Citation: Póvoa PR, Carneiro AH, Ribeiro OS, Pereira AC, Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study). Crit Care Med. 2009;37(2):410-416.

Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients

Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?

Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.

However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.

Study design: Randomized, placebo-controlled trial.

Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.

Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”

Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.

Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.

Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.

Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria

Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?

Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.

Study design: Retrospective cohort study.

Setting: A single-site Veterans Affairs hospital.

Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.

In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.

This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.

An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.

Bottom line: A clinical determination of whether a patient with a catheter really has a symptomatic UTI/urosepsis or only has asymptomatic bacteriuria should precede starting antibiotics in hospitalized patients.

Citations: Cope M, Cevallos ME, Cadle RM, Darouiche RO, Musher DM, Trautner BW. Inappropriate treatment of catheter-associated asymptomatic bateriuria in a tertiary care hospital. Clin Infect Dis. 2009;48(9):1182-1188.

Kunin CM. Catheter-associated urinary tract infections: a syllogism compounded by a questionable dichotomy. Clin Infect Dis. 2009;48:1189-1190.

Current Practices in the Evaluation and Management of Thrombocytopenia in Heparin Patients

Clinical question: Are the current American College of Chest Physicians (ACCP) guidelines for the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) being followed?

Background: Heparin-based anticoagulation is frequently given to hospitalized patients, and approximately 1% to 5% of these patients develop HIT. In 2004, the ACCP published a consensus statement on the evaluation, management, and prevention of HIT.

Study design: Prospective, observational study.

Setting: Forty-eight U.S. hospitals in the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

Synopsis: The CATCH trial enrolled patients receiving any form of heparin for >96 hours (n=2,420), cardiac-care-unit patients treated with heparin (n=1,090), and patients who had an HIT antibody assay performed (n=449), for a total of 3,536 total patients. The study included patients on unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Thrombocytopenia was defined at a platelet count <150,000, or a decrease of 50% when compared with admission.

In the prolonged heparin group, 36.4% of patients developed thrombocytopenia; however, HIT was suspected in only 19.8% of these high-risk patients. While physicians were more likely to consider HIT in the cardiac-care patients (37.6%), the diagnosis was considered>24 hours after the thrombocytopenia developed. Physicians often waited until after a thromboembolic complication occurred before evaluating for HIT. More often than not, preventive measures were missed (e.g., failing to check for HIT antibodies, continuing heparin after HIT was suspected).

Bottom line: Thrombocytopenia is a common occurrence in patients receiving heparin and, despite the risk of devastating complications from HIT, treatment infrequently conforms to the established guidelines.

Citation: Crespo EM, Oliveira GBF, Honeycutt EF, et al. Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J. 2009;157(4):651-657. TH


Epinephrine and Dexamethasone Alone Do Not Reduce Hospital Admissions in Infants with Bronchiolitis

By Mark Shen, MD

Clinical question: Does nebulized epinephrine, oral dexamethasone, or a combination of the two result in a decrease in hospital admissions when given in the ED to infants with bronchiolitis?

Background: Bronchiolitis is the most common lower-respiratory-tract infection of infancy. Rates of admission have climbed in the past two decades. Bronchodilators and corticosteroids are not routinely recommended, and the evidence surrounding epinephrine and dexamethasone has shown varying results.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Eight Canadian pediatric EDs.

Synopsis: Eight hundred infants ages six weeks to 12 months with a first episode of bronchiolitis were randomized to nebulized epinephrine and oral dexamethasone, epinephrine and oral placebo, dexamethasone and nebulized placebo, or oral and nebulized placebo. Epinephrine was delivered as two nebulizations 30 minutes apart, and dexamethasone was given as a 1 mg/kg oral dose, followed by five once-daily doses of 0.6 mg/kg. In unadjusted analysis, only the infants who received epinephrine and dexamethasone were less likely to be admitted to the hospital by day seven.

Limitations of this study include a small effect size and a non-statistically-significant difference between the epinephrine/dexamethasone group and placebo after statistical adjustment for multiple comparisons. Given that admission rates did not decrease in the epinephrine/placebo group and the dexamethasone/placebo group, this study supports national guidelines that do not recommend the routine use of these agents in bronchiolitis. The authors suggest that synergy between epinephrine and dexamethasone in bronchiolitis be further studied.

Bottom line: When given alone, epinephrine and dexamethasone do not reduce hospital admissions in infants with bronchiolitis.

Citation: Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):2079-2089.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

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